Oncologists Use Monoclonal Antibody to Improve the Outcome of Bone Marrow Transplantation at Rush-Presbyterian-St. Luke's Medical Center
A monoclonal antibody may allow more patients with the most common type of leukemia, chronic lymphocytic leukemia (CLL), to use their own bone marrow to treat the disease and may prolong their disease-free survival, according to researchers at Rush-Presbyterian-St. Luke's Medical Center, Chicago.
Rush is one of only 12 medical centers in North America studying the effectiveness of the monoclonal antibody, Rituxan (rituximab), as part of a new in-vivo purging process to rid blood stem cells -- immature cells from which all blood cells develop-- of leukemia in autologous (using the patient's own bone marrow) transplantation.
"Improving the effectiveness of autologous transplants can offer new hope for many leukemia patients," says Dr. Hans Klingemann, director of bone marrow transplantation at Rush-Presbyterian-St. Luke's Medical Center. "A process that effectively cleanses leukemia in autologous transplants has been the missing link in prolonging disease-free survival for patients with CLL. We may have found the answer."
Dr. Leanne Berkahn, principal investigator of the Rituxan study and assistant professor of medicine at Rush, and Dr. Klingemann have treated three patients with the monoclonal antibody and have found that it reduces leukemia to a low level that can be effectively controlled by the body's own immune system.
"Nearly 70 percent of leukemia patients are not eligible for transplants because of their age or because a sibling donor isn't available, so it's critical to identify treatments that will allow more patients to use their own marrow," says Dr. Berkahn. "In addition, the complication rate from donor transplants is about 25 percent compared with a 5 percent complication rate for autologous transplants."
"With autologous transplants, the challenge lies in giving patients a disease-free transplant, and, until now, that hasn't been possible using the patient's own marrow." " In addition, improvement in the support care of bone marrow transplantation means that people up to 65 years of age will be able to undergo this procedure with increased safety. We hope that this new treatment will give patients a transplant virtually free of leukemia, a transplant equivalent to that of healthy donor."
Leukemia is a progressive disease of the blood that results from a change in the DNA of a single cell in the bone marrow. The affected cell transforms into a leukemic marrow cell that has a growth and survival advantage in the marrow. With CLL, the change in the bone marrow cell produces lymphocytes, a type of white blood cell. The lymphocytes multiply and gradually crowd normal white blood cells in the lymph nodes and other sites in the body that reduces the ability of the remaining healthy cells to fight infection.
CLL can be controlled for many months or even years with chemotherapy, but studies show in virtually all patients, the leukemia returns. "Following chemotherapy it is just a matter of time before the leukemia will come out of remission," says Dr. Berkahn. "That's why transplantation using a healthy marrow has been a more effective treatment because the patient is actually receiving healthy, disease-free cells."
In the new treatment study at Rush, patients are hospitalized for two to three weeks to undergo intensive chemotherapy. High doses of chemotherapy are given over a four-hour period to decrease the number of leukemia cells in the blood so a sufficient amount of non-diseased blood stem cells can be collected for transplantation. After chemotherapy, a blood cell stimulating hormone is given by injection to enhance the patient's blood count. Then the patient's blood is passed through a machine that separates the stem cells from the blood and returns the blood to the patient. This process, called leukapheresis, usually takes between four and six hours.
Since the collected stem cells may still contain some leukemic cells, the patient will receive a single injection of the monoclonal antibody, Rituxan, the day after the first stem cell collection. After one day of rest, Rituxan has time to kill the leukemic cells and a second stem cell collection takes place.
"We have seen a dramatic reduction in the amount of leukemic cells in the second harvesting in the initial patients that we have treated," says Dr. Klingemann. "The second set of stem cells is purged of disease within the body and these 'clean' cells are the ones that are given back to the patient."
Once the cells are collected after treatment with Rituxan, they are frozen in liquid nitrogen until the patient has received another treatment of chemotherapy. The purpose of additional chemotherapy is to kill all potentially remaining leukemia cells in the body before transplanting the previously collected disease-free stem cells. Radiation therapy is administered to the entire body over three days and chemotherapy is given over the next two days.
After one day of rest, the stem cells are thawed and given to the patient in a process similar to a blood transfusion. After infusion, the marrow travels through the bloodstream into the bone marrow spaces, where the stem cells grow, divide and begin to produce new red blood cells, white blood cells and platelets.
"This a very promising treatment for a disease that was once thought to be incurable," says Dr. Berkahn. "The first patients treated with antibody had no evidence of disease after the transplant even when very sensitive methods of detection were used."
According to the Leukemia Society of America, more than 8,500 new CLL cases are diagnosed every year in the United States. It is considered a disease of middle or old age; at diagnosis, approximately ninety percent of all CLL patients are over age fifty and the incidence increases with age.
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